(1) Field of the Invention
This invention relates to a novel anticoagulating substance and a preparation process thereof.
(2) Description of the Prior Art
The coagulation of blood is considered to start with the development of thromboplastin activity, followed by activation of factors X and V in the blood, further activation of prothrombin into thrombin and final conversion of fibrinogen into fibrin by the action of the thrombin.
For the treatment of diseases ascribed to the coagulation, it is effective to use a substance which is able to impede or deactivate various coagulation factors which take part in the coagulation mechanism, i.e. An anticoagulating substance. Currently known anticoagulating substances include heparin, heparin cofactor-II, antithrombin-III, .alpha..sub.2 -macroglobulin, .alpha..sub.1 -trypsin inhibitor, C.sub.1 -esterase inhibitor, protein C and the like. Recently, Chris P. M. Reutelingsperger, et al. found out, as reported in Eur. J. Biochem., 151, 625-629 (1985), a novel substance having anticoagulating activity and a molecular weight of 32 kDa from umbilical arteries.
However, most of these anticoagulating substances have been confirmed merely to exist and it is only heparin that is now in use as a medicine. Since heparin has a side effect to induce bleeding, strict limitations are however imposed on the manner, amount, etc. of its use. Thus, it is not satisfactory as an anticoagulating agent from the standpoint of safety.
The substance found by Reutelingsperger, et al. is different from the substance of the invention as will be described subsequently. In addition, the activity of the substance has been determined only in the form of a mixture and thus, such a substance is by no means considered to be useful for practical services.
There has hence been a demand for the development of a better anticoagulating agent.
The present inventors previously carried out an extensive investigation with a view toward developing an anticoagulating agent which is safe and is free of side effects. As a results, it was found that a novel anticoagulating substance is obtained from a placenta, which contains a large amount of tissue thromboplastin along with the factor XIII and the fibrinolytic inhibition factor, is considered to have a tendency toward thrombotic formation and is in a special state from the standpoint of the coagulating mechanism, especially, a sediment obtained by centrifuging a human placenta homogenate or a microsome fraction obtained by fractionating the supernatant of the centrifugation. An application for a patent has already been filed based on the finding (U.S. Pat. Application Ser. No. 909,296 filed September 19, 1986).